Nucleic acids encoding antibodies against PD-1

• US 8,088,905 B2
• Filed: 03/16/2009
• Issued: 01/03/2012
• Est. Priority Date: 12/23/2002
• Status: Expired due to Fees

• Current Assignee: MedImmune Ltd. (Astrazeneca PLC), Wyeth (Pfizer Inc.)
• Original Assignee: MedImmune Ltd. (Astrazeneca PLC), Wyeth (Pfizer Inc.)
• Inventors: Collins, Mary, Wood, Clive R., Carreno, Beatriz M., Luxenberg, Deborah, Jussif, Jason, Carter, Laura L., Bennett, Frances K., Andrews, John, Russell, Caroline, Valge-Archer, Viia
• Primary Examiner(s): OUSPENSKI, ILIA I
• Application Number:
  US12/405,058
• Publication Number:
  US 20100028330A1
• Time in Patent Office: 1,023 Days
• Field of Search: None
• US Class Current: 536/23.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 16/2803 against the immunoglobulin superfamily
• CPC Class Codes: C07K 16/2818 against CD28 or CD152
• CPC Class Codes: C07K 2317/622 Single chain antibody (scFv)
• CPC Class Codes: C07K 2317/73 Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding

Abstract

This disclosure provides antibodies and antigen-binding fragments that can act as agonists and/or antagonists of PD-1 (Programmed Death 1), thereby modulating immune responses in general, and those mediated by TcR and CD28, in particular. The disclosed compositions and methods may be used for example, in treating autoimmune diseases, inflammatory disorders, allergies, transplant rejection, cancer, and other immune system disorders.

Claims

1. An isolated nucleic acid encoding an antibody comprising:

(i) a V_H domain that comprises three CDRs having the amino acid sequences as set out in;

(a) SEQ ID NOs;

23, 24, and 25,

(b) SEQ ID NOs;

29, 30, and 31,

(c) SEQ ID NOs;

35, 36, and 37, or

(d) SEQ ID NOs;

50, 51, and 52;

or

(ii) a V_L domain that comprises three CDRs having the amino acid sequences as set out in;

(e) SEQ ID NOs;

26, 27, and 28,

(f) SEQ ID NOs;

32, 33, and 34,

(g) SEQ ID NOs;

38, 39, and 40, or

(h) SEQ ID NOs;

53, 54, and 55,

wherein the antibody specifically binds an epitope within the extracellular domain of human or mouse PD1.

2. An expression vector comprising the nucleic acid of claim 1.

3. An isolated host cell comprising the vector of claim 2.

4. The nucleic acid of claim 1, wherein the V_H domain comprises the amino acid sequence SEQ ID NO:

6, 10, 14, or 47; and

the V_L domain comprises the amino acid sequence SEQ ID NO;

8, 12, 16, or 49.

5. The nucleic acid of claim 4, wherein the nucleic acid comprises a nucleotide sequence selected from the group consisting of

(a) SEQ ID NOs:

5, 9, 13, and 46;

or

(b) SEQ ID NOs;

9, 11, 15, and 48.

6. A method of making an antibody that specifically binds with PD-1, the method comprises:

(a) providing the expression vector of claim 2;

(b) expressing the antibody encoded by the expression vector in a host cell; and

(c) recovering the antibody.